Esters of salicylic-acid derivatives and process of making the same.



To all-whom it may concern:

doctor of German Empire,

.ri't iirnn reinsur- Qhi lslQE.

NATHAN SULZBEBGER, BERLIN,

nun SPIEGEL, or CHARLOTTENBURG GERMANY.

TESTERS BF SALICYLIGACED DERIVATIVES AND Pit-GUESS 01* MAKING THE SAME.

sewer.

No Drawing.

Be it known that we, NATHAN Sunscreens, philosophy, chemist, a citizen of the United States, residing at39 Unter den Linden, Berlin, Kingdom of Prussia,

and Lnoeonn SrnionL, doc- "tor of philosophy, private decent ofchemis- University, a subject of ing' at 24 Schliiterstrasse, Qharlottenburg, Kingdornof Prussia, German Enipire, have jointly invented new and useful Improvements in Esters 0f Salicylic-Acid Deriva-= fives and Processes of Making the Same, of which the following is a specification.

The object of our invention is to inake compounds of salicylic acid which are easilyiand without any irritating; action absorbed "by the skin and are decomposed within the organism with liberation of salicylic acid.

Our process consists in combining derivatives of'salicylic acid, containing the free phenolic group but in which the-hydroxylic group o::t' the carboxylic group is substituted by other groups, with aliphatic acids con taln'infg more than 12 atoms of. carfbon in their" rnolecule, with-elimination of water.

By this reaction esterlike compounds of salicylic acid with the said aliphatic acids will be produced; the phenol group-of the salicylic acid (or its derivatives) reacting I with the carboxylic group of the aliphatic acids. J V

As. derivatives of sal cylic acid, we 1 use derivatives of salicylic acid in which the hydroxyl oft-he carhoxylic group has been 1 replaced by other groups, in order to ayoid involving the carbonylic group in the re action. l Ve may use the esters of the salicylic acid with alcohol radicals. The skilled workman will find the compounds suitable for his purpose by experiments. If we use condensing agents containing halogen, we

prefer to employ the-salts ofthe'aliphatic ess or to avoid and diminish 'We heat. a mixture 'of'332 acids instead of the free acids in order to neutralize the free acids evolved in'th'e procthe formation of them. 7 I z In order to enable the skilled workman to carry out our invention we describe as an example the manufacture of the oleyl sali cylic ethyl ester oleyl meaning the grou (3 11 30, whereas the oleic acid is C H O grains salicylic Specification of Batters Patent.

finished more ethyl ester, 608 grams oleate of sodium and Patented. Mar. 28, Troll. Serial no. 26 3,2317. i 153.5 grains ozry-chlorid of phosphorus in suitable vessel to a temperature of about 100 degrees centigrade untilthe reaction is finished. W e may also use higher temperatures, in which case the reaction will be quickly. The reaction may be representedby the following equation:

zds om coiciso. aoeseoma Pool;

Se icyhc acid. Olecte of O chlorid of ethyl ester. sodium. fiosphorus. ZC HAOQC BM){CO CaHs} NaCl 2HC1 NaPO Qleylsahcyhc acid Chlon'd of Hydro- Metaphosethyl ester. 1 v sodium. chloric photo of acid. sodium.

We may also use free oleic acid instead of the sodium oleate. In this case We use 564 grains oleic acid instead of the 608 grams oleate of sodium quoted in the above de scribed example. In order to neutralize the acid, that may be formed during the reac tion, we prefer to add to the mixture neutralizing agents having no sapon'itying actlen', as for instance carbonate of calcium. we use for instance 200 gramsicarbonate of calcium, if we employ the above quoted proportions. Of course we may also employ larger or smaller quantities of the neutralizing agents. In order to separate the by-prodnote from the desired compound, We ma wash the product of the reaction with water. The oleyl salicylic ethyl ester purified in the described manner has the composition (3 11 0,, as in the analysis we have found the following proportionf C=74c.81% (calculated 75.29%) E 210.32 (calculated 9.8 5%").

The above quoted proportions of the coinponents for manufacturing our newproducts give essentially oleyl salicylic acid ester. We may, however, change the proportions, so that we use a surplus of oleic acid or asurplus of salicylicacid-or their derivatives.

V7 e obtain then mixtures of the oleyl salicylic acid ester with oleic acid or with salicylic acid ester. plus by heating ingthe first casecalcinm, bariiun, or such like, in the second. case by shortly blowing off with steam the 'uncoinloined salicylic acid 88%)).5'0118 1118? the product of thereaction also use the product of the reaction contain-I ing surplus of one of the components without a separation of the surplus. The condensing agent can be used in the amount required by by the equation above quoted. We may however use larger 0 1 smaller proportions. One

mayv mix the whole quantity of thecondens {hie-can separate the said suitwith alkaline carbonates of.

the theory represented ingj agent used with the components or. may

add the cond 'nsin agent gradually.

The oleyl s licy ic acid; ethyl esteris an oily mass, solidifies when cooled and-melts easily 'absorbed'by the skin without having an ,irritating 'actlon and is decomposed in the organism, with liberation of: salicylic acid. It'is' soluble in oils and fats, is non volatile,.doe s-f1not decompose" carbonates.

' Instead of. the salicylic acid ethyl ester, one may use other-esters'ofthis acid or other derivatives of .the salicylic acid containing the free 'phenolgroup, wherein-the carboxyl-ic group issuitably changed so as to revent'it from taking part in the reaction In the place of the oleic acid one may'also tether fatty acids as erucic acid, bras? l aidic, ricinoleic, palmitic, stearic lensing agents, is, when purified in-the man -ner described'for oleyl salicylicac'id ethyl ester, a white crystalline mass of the COIliposition I G -.74.89% C, 10.78%}1 corresponding to the formula:

c H/ a 1 O.COCnHa5 I It melts at about 48 to i9 One may also use mixturesv of the said acids, for instanceas one may obtain themby saponifying fats and oils.

The,resultingpompound have" oily con;

'- sistency or aresolid subst nces, soluble in oil and fats. different sub tances, as lycopodium, starch One may mix them with inmeal, e'tc., in order to prepare dusting powders. ,They have antiseptic action. The compounds of our invention may also be used "as v cosmetical and pharmaceuticah preparations either alone or mixed with 'oils,

fats, indifferent substances, either internally or externally.

-What we claim'as our invention and de 3 jsire to secure byLetters Patent is 1.' The process of manufacturing ester like compounds of aliphatic acidswith' salicylic acid derlvatives which consists in heat- I aliphatic acid haying more than 12'at0msmg to ethercondensing agents, and an :the carboxylic group has been replaced by a neutral groupand the phenol hydroxyl then at about '10 degrees oentigrade. It is- I v to.-- The stearyl' salicylic acid ethyl ester prepared by heating salicylic ethyl ester andstearic acid with or without con- .ROOO/H, containing more of carbon'with derivatives of salicylic acid in which the hydrogen of. the hydroxyloi I remains unchanged v 2. The process a of manufacturing j esterlike compounds of aliphatic acids with sa]i-. cylic acidtwhi'ch consists in heating. together condensing agents, substances the to neutralize ac1ds';and an aliphatic acid having more thanv i2.-atoms of carbon with derivetiv'es of salicylic'acid in which the hydrogen of the hydroxyl of the carboxylivgrouplas 8 hydroxyl remains unchanged.

- *3; The process of manufacturing oleyl salicylicalkyl ester which consists in heat ingsalicylic alkyl ester with oleic acid and condensing agents.

{L 'Asnew' arti'c of salicylic'acid derivatives with aliphatic acids, having morethan' 12 atoms of carbon in the molecule, said esters having the general formula:

in which formula X means a neutral group substitutingthe hydrogen of the car- ,boxylic hydroxyl of salicylicacid, and

X R'COO, the radical of an aliphatic acid,

les of manufacture esters 4 than -12 atoms of carbon, soluble in oils and fats, not

volatile, being decomposed by alkalis into salicylic acid and fatty acid, which esters i are absorbed by the skin without an irritatin'g action and are decomposed'inthe organism with liberation of salicylic acid;

5. As new article of manufacture oleyl salicylic acid ethyl ester being at ordinary temperature an oil melting at about 10 degrees centigrade solidifying below 0 degrees Centigrade, soluble-in oil, and fats, not volatile, being decomposed by alkalis into salicylic'acid and oleic acids,

In testimony whereof we have signed our names'to this specification-in the presence of two subscribing witnesses.

NATHAN sULz'BEneEn. LEOPOLD SPIEGEL.

-Witnesses HENRY HASPER, WOLDEMAR Go'piesfotthis patentmay be obtained for five cents each, by addressing the' Commissioner of Eatents, 

